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Research paper
Increased mortality persists in an adult drug-resistant epilepsy prevalence cohort
  1. Brian Callaghan1,
  2. Hyunmi Choi2,
  3. Malka Schlesinger2,
  4. William Rodemer3,
  5. John Pollard3,
  6. Dale C Hesdorffer2,
  7. W Allen Hauser2,
  8. Jacqueline French4
  1. 1Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
  2. 2Columbia University, New York, New York, USA
  3. 3Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  4. 4New York University, New York, New York, USA
  1. Correspondence to Dr Brian Callaghan, Department of Neurology, University of Michigan, 109 Zina Pitcher Place, 4021 BSRB, Ann Arbor, MI 48104, USA; bcallagh{at}


Objective To investigate the cumulative probability of death and the standardised mortality ratio (SMR) in an adult drug-resistant epilepsy (DRE) population.

Methods In two separate centres during 2003–2006, we identified a total of 433 patients with DRE defined as at least one seizure per month and failure of at least two antiepileptic drugs. These patients were subsequently followed for a total follow-up of 6 years. We examined the cumulative probability of death, using Kaplan-Meier methodology, and the SMR based on mortality data from the Social Security Death Index. Clinical predictors of death were evaluated using Cox regression analysis.

Results The cumulative probability of death was 8.7% (95% CI 6.2% to 12.1%) at 6 years. The overall SMR was 2.4 (95% CI 1.7 to 3.3). It was 3.1; 95% CI 2.0 to 4.6 in subjects with remote or progressive aetiology and 1.7; 95% CI 0.8 to 2.8 in subjects with unknown aetiology. The SMR was significantly increased in those with a known remote aetiology (2.5; 95% CI (1.4 to 3.8)). Older age at enrolment and symptomatic generalised epilepsy syndrome were significant predictors of death.

Discussion Mortality is increased in this drug-resistant population; largely driven by those with a known epilepsy aetiology. The increased mortality remains even after exclusion of those with a progressive aetiology. Previous studies of incident epilepsy cohorts revealed increased mortality that declines to near-normal levels after the first several years, but in our DRE cohort, mortality remains elevated despite a median duration of epilepsy of 25 years at study entry.

  • Epilepsy
  • Neuroepidemiology
  • Anticonvulsants

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